Tumor angiogenesis: from molecular mechanisms to targeted therapy
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| Format: | Buch |
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| Sprache: | English |
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Weinheim
Wiley-VCH
2010
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| Schlagworte: | |
| Online-Zugang: | Inhaltstext Inhaltsverzeichnis Klappentext |
| Beschreibung: | XXII, 329 S. Ill., graph. Darst. |
| ISBN: | 9783527320912 3527320911 |
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| 245 | 1 | 0 | |a Tumor angiogenesis |b from molecular mechanisms to targeted therapy |c ed. by Francis S. Markland ... |
| 264 | 1 | |a Weinheim |b Wiley-VCH |c 2010 | |
| 300 | |a XXII, 329 S. |b Ill., graph. Darst. | ||
| 336 | |b txt |2 rdacontent | ||
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Datensatz im Suchindex
| _version_ | 1805093907845873664 |
|---|---|
| adam_text |
Contents
Prefece
XV
List of Contributors
XIX
Part
1
Introduction
1
1
Overview on Tumor Angiogenesis
3
Maria
Benedetta Donati
and Roberto Lorenzet
1.1
Once upon a Time.
. 3
1.2
A Challenge Across Two Centuries: Inhibition of Angiogenesis to Stop
Tumor Growth
4
1.3
Clinical Implications of Angiogenesis Inhibition
5
1.4
Angiogenesis: A Novel Bridge between Malignancy and
Thrombosis
6
1.4.1
The Association between Human Cancer and the Clotting System
7
1.4.2
The Role of TF in Physiologic and Tumor Angiogenesis
S
1.5
Conclusions
9
Acknowledgments
10
References
10
Part II Mechanisms of Angiogenesis and Lymphangiogenesis
15
2
Molecular Mechanisms of Angiogenesis
17
Andrew C. Dudley and Lena Claesson-Welsh
2.1
Vessel Formation
17
2.1.1
Vasculogenesis
18
2.1.2
Circulating Endothelial Progenitor Cells
18
2.1.3
Intussusception
18
2.1
A Sprouting Angiogenesis
19
2.2
Factors That Stimulate Blood Vessel Formation
19
2.2.1
Vascular Endothelial Growth Factors (VEGFs)
19
2.2.2
Fibroblast
Growth Factors (FGFs)
20
2.2.3
Platelet-Derived Growth Factors (PDGFs)
21
VI
I Contents
2.2.4
Angiopoietins (Ang's)
21
2.3
Molecular Targets in the Therapeutic Inhibition of Angiogenesis
22
2.3.1
Anti-VEGF Therapies
23
2.3.2
Evidence for Refractoriness to Anti-VEGF Strategies
24
2.4
Other Impediments to Antiangiogenic Therapies
24
2
A.I Hallmarks of Dysregulated Tumor Angiogenesis
25
2.4.2
Tumor Vessel Normalization
26
2.4.3
Tumor Endothelial Cell Abnormalities
26
2.5
Future Perspectives
27
References
28
3
Proangiogenic Factors
35
Domenico Ribatti
3.1
Introduction
35
3.2
"Classic" Proangiogenic Factors
36
3.2.1
Vascular Endothelial Growth Factor
36
3.2.2
Fibroblast
Growth Factor^
38
3.2.3
Transforming Growth Factor
β
and Platelet-Derived
Growth Factor
β
38
3.2.4
Angiopoietins
39
3.3
"Nonclassic" New Proangiogenic Factors
40
3.3.1
Erythropoietin
40
3.3.2
Angiotensin-II
41
3.3.3
Endothelins
41
3.3.4
Adrenomedullin
42
3.3.5
Leptin
42
3.3.6
Adiponectin and Neuropeptide-Y
43
3.3.7
Vasoactive Intestinal
Peptide
and Substance-P
43
3.4
Conclusions and Perspectives
44
Acknowledgments
45
References
45
4
The Role of Accessory Cells in Tumor Angiogenesis
53
Nobuyuki
Takakura
4.1
Introduction
53
4.2
Developmental Association of Vascular Cells and Hematopoietic
Cells
55
4.3
Inflammation and Cancer
58
4.4
Hematopoietic Cells Promote Angiogenesis as an Accessory Cell
Component
59
4.4.1
Mast Cells
(MC) 59
4.4.1.1
Physiological Function
59
4.4.1.2
Localization in the Tumor Environment and Recruitment
to Tumors
60
4.4.1.3
Functions in Angiogenesis
61
Contents
VII
4.4.2 Monocyte/Macrophage
Lineage Cells
62
4.4.2.1
Physiological Function
62
4.4.2.2
Localization in the Tumor Environment and Recruitment
to Tumors
62
4.4.2.3
Functions in Angiogenesis
63
4.4.3
Tie 2-Expressing Monocytes
(ТЕМ)
64
4.4.3.1
Physiological Function
64
4.4.3.2
Localization in the Tumor Environment and Recruitment
to Tumors
64
4.4.3.3
Functions in Angiogenesis
64
4.4.4
Myeloid-Derived Suppressor Cells (MDSCs)
65
4.4.4.1
Physiological Function
65
4.4.4.2
Localization in the Tumor Environment and Recruitment
to Tumors
65
4.4.4.3
Functions in Angiogenesis
65
4.4.5
Neutrophils
66
4.4.5.1
Physiological Function
66
4.4.5.2
Localization in the Tumor Environment and Recruitment
to Tumors
66
4.4.5.3
Functions in Angiogenesis
67
4.4.6
Eosinophils
67
4.4.6.1
Physiological Function
67
4.4.6.2
Localization in the Tumor Environment and Recruitment
to Tumors
68
4.4.6.3
Functions in Angiogenesis
68
4.4.7
Dendritic Cells (DCs)
68
4.4.7.1
Physiological Function
68
4.4.7.2
Localization in the Tumor Environment and Recruitment
to Tumors
68
4.4.7.3
Functions in Angiogenesis
69
4.4.8
Hematopoietic Stem Cells (HSCs)
69
4.4.8.1
Physiological Function
69
4.4.8.2
Localization in the Tumor Environment and Recruitment
to Tumors
69
4.4.8.3
Functions in Angiogenesis
70
4.5
Clinical Therapeutic Applications
70
4.6
Conclusions
71
References
72
5
Comparison between Developmental and Tumor Angiogenesis
85
Andreas Bikfalvi
5.1
Introduction
85
5.2
Vascularization by Sprouting Angiogenesis
85
5.3
Intussusceptive Vascular Growth
89
5.4
Vasculogenesis and Angioblast Recruitment
90
VIII Contents
5.5
Cooptíon
91
5.6
Other Mechanisms of
Vasoformation
92
5.7
Developmental Angiogenesis and Tumor Angiogenesis: Similar and
Different
92
Acknowledgments
93
References
93
6
Tumor Lymphangiogenesis
97
Swapnika Ramu and Young-Kwon Hong
6.1
Development of Lymphatic System
97
6.2
Tumor Lymphangiogenesis
99
6.3
Role of the VEGF-C/VEGF-D/VEGFR-S Signaling Axis in Tumor
Lymphangiogenesis
102
6.4
Cross Talk between Angiogenesis and Lymphangiogenesis
105
6.5
Role of Other Factors
106
6.5.1
VEGF-A
106
6.5.2
PDGF-BB
106
6.5.3
Hepatocyte Growth Factor
107
6.5.4
Insulin-Like Growth Factors
107
6.5.5
Angiopoietins
107
6.5.6
Fibroblast
Growth Factor-2
108
6.5.7
Chemokines
108
6.5.8
Other Factors
109
6.6
Lymph Node Lymphangiogenesis
110
6.7
Therapeutic Implications
110
6.8
Summary
113
References
113
Part HI Signal Transduction and Angiogenesis
125
7
Integrin
Involvement in Angiogenesis
127
Abebe Akalu, Liangru Contois, and Peter
С
Brooks
7.1
Introduction
127
7.2
Sprouting Angiogenesis
128
7.3
Cellular Regulators of Angiogenesis
129
7.4
Molecular Regulators of Angiogenesis
130
7.5
Integrins
and Angiogenesis
131
7.6
Integrin
Structure
132
7.7
Integrin
Binding and Bidirectional Signaling
133
7.8
Involvement of
Integrins
in the Initiation Phase of Angiogenesis
135
7.9
Integrin
and Growth Factor Interactions in Angiogenesis
135
7.10
Integrin
and Growth Factor Receptor Interactions in
Angiogenesis
136
7.11
Integrin-Mediated Regulation of Cell Adhesion
137
7.12
Integrin-Mediated Regulation of Protease Expression
138
Contents
І
IX
7.13
Involvement of
Integrins
in the Invasive Phase of Angiogenesis
139
7.14
Involvement of
Integrins
in Protease Activation and Cell Surface
Localization
139
7.15
Involvement of
Integrins
in the Maturation Phase of
Angiogenesis
141
7.16
Conclusions
142
Acknowledgments
143
References
143
8
Signaling Pathways in Tumor Angiogenesis
153
Cristina
Abrahams,
Christopher
Daly, Alexandra
Eichten,
2he Li,
Irene Noguera-Troise, and Gavin Thurston
8.1
Introduction
153
8.2
VEGF Pathway
154
8.2.1
Receptors, Ligands, and Signaling Pathway
154
8.2.2
Requirement for VEGF Pathway during Early
Embryogenesis 155
8.2.3
Multiple Roles of VEGF Signaling in Tumor Angiogenesis
156
8.2.4
VEGF as a Therapeutic Target
157
8.3
Delta-Notch Pathway
159
8.3.1
Receptors, Ligands, and Signaling Pathway
159
8.3.2
Requirement for Delta-Notch Pathway during
Embryogenesis 160
8.3.3
Role of Delta-Notch Signaling in Tumor Angiogenesis
161
8.3.4
Delta-Notch as a Therapeutic Target
161
8.4
Angiopoietin-Tie Pathway
161
8.4.1
Receptors, Ligands, and Signaling Pathway
161
8.4.2
Requirement for Angiopoietin-Tie Pathway during
Embryogenesis 163
8.5
Ang-1 as a Promoter of Vascular Stability/Quiescence
163
8.5.1
Is Ang-2 a Proinflammatory, Vascular Destabilizing Factor or a
Protective Factor?
164
8.5.2
Angiopoietins in Tumor Angiogenesis
165
8.6
TGF-jS Pathway
166
8.6.1
Receptors, Ligands, and Signaling Pathway
166
8.6.2
Requirement for
TGF-ß
Pathway during
Embryogenesis 166
8.6.3
Predinical and Clinical Data on
TGF-ß
Pathway in Tumor
Angiogenesis
167
8.7
Ephrin-Eph Pathway
167
8.7.1
Receptors and Ligands
167
8.7.2
Eph—Ephrin Receptor—ligand Bidirectional Signaling 16S
8.7.2.1
EphrmA-EphA
169
8.7.2.2
EphrinB-EphB
169
8.8
Summary and Conclusions
170
References
170
Χ Ι
Contents
Part IV Therapeutic Approaches and Angiogenesis
179
9
Development of an Integrin-Targeted Antiangiogenic Agent
181
Stephen Swenson,
Radu
Minea,
and Francis S.
Markland
9.1
Toward Molecular Treatment of Cancer
182
9.2
Disintegrins as Molecular Weapons against Cancer
184
9.3
Recombinant
Expression of a Venom-Derived Disintegrin
185
9.4
Functional In vitro Evaluation of VN
187
9.4.1
Integrin
Binding
287
9.4.2
Binding Affinities of VN to
Integrins
188
9.4.3
Inhibition of Cellular Processes Critical to Tumor Progression
189
9.4.4
Inhibition ofHUVEC Tube Formation
190
9.4.5
Nanosomal Encapsulation of VN
191
9.5
Functional In vivo Evaluation of VN
193
9.5.1
Circulatory Half-life of LVN
193
9.5.2
In vivo Biological Assay
193
9.6
Antiangiogenic Effect of LVN Therapy
196
9.6.1
Tumor Tissue Harvest, Sectioning, Fixation, and Staining
196
9.6.2
Immunohistochemical (IHC) Staining
196
9.6.3
Evaluation of Tumor-Induced Blood Vessel Growth
197
9.7
Toxicology Studies
199
9.8
Summary
199
References
202
10
Anti-VEGF Approaches and Newer Antiangiogenic Approaches Which
Are Already in Clinical Use
207
Chandu Vemuri and Steven K. Libutti
10.1
Introduction
207
10.2
Discovery of VEGF
207
10.3
Anti-VEGF Cancer Therapeutics
210
10.3.1
Monoclonal Antibodies
210
10.3.1.1
Discovery and Development of Bevacizumab (Avastin®)
210
10.3.1.2
Clinical Trials
211
10.3.1.3
Phase I and Phase II Trials
211
10.3.2
Metastatic Colorectal Cancer
212
10.3.2.1
First-line Therapy
212
10.3.2.2
Second-line Therapy
212
10.3.3
Metastatic Renal Cell Cancer (mRCC)
213
10.3.4
Non-Small Cell Lung Cancer (NSCLC)
213
10.3.5
Recurrent Glioblastoma
Multiforme
213
10.3.6
Breast Cancer
214
10.4
Other Anti-VEGF Approaches
214
10.4.1
Small Molecule Tyrosine Kinase Inhibitors
214
10.4.1.1
Sorafenib (Nexavar®)
214
10.4.1.2
Sunitinib (Sutent®)
216
Contents
XI
10.5 Non-VEGF
Antíangiogenic
Agents in Clinical Use
216
10.5.1
Monoclonal Antibodies
217
10.5.1.1
Cetuximab
217
10.5.2
Small Molecule Tyrosine Kinase Inhibitors (smTKI)
218
10.5.2.1
Erlotinib
218
10.5.3
Inhibitors of Mammalian Target of Rapamycin (mTOR)
219
10.5.3.1
Discovery
219
10.5.3.2
Advanced Renal Cell Carcinoma
220
10.6
Future Direction of Antiangiogenesis Therapies
220
References
221
11
Combination of Antiangiogenic Therapy with Other
Anticancer
Therapies
227
Raffaele
Longo,
Francesco Torino, and Giampietro Gasparini
11.1
Introduction
227
11.2
Antiangiogenic Therapy and
Immunomodulation 228
11.3
Anti-VEGF and Anti-EGFR/HER^ Combinations
231
11.4
Miscellaneous Anti-VEGF Combinations
234
11.5
Antiangiogenic Therapy and Radiation Treatment
237
11.5.1
Biological Aspects
237
11.5.2
Combination of Angiogenesis Inhibition with Radiotherapy:
Preclinical Evidence
239
11.5.3
Antiangiogenic Therapy with Radiation or Chemoradiation Therapy:
Clinical Trials
240
11.6
Challenges of Study Design for Combined Antiangiogenic
Therapy
243
References
244
12
Tumor Specificity of Antiangiogenic Agents
255
Olivier Rixe, RonanJ. Kelly, and Giuseppe
Giaccone
12.1
Introduction
255
12.2
Tumor Specificity
256
12.2.1
VEGF Expression in the Adult
256
12.2.2
Function of VEGF in the Adult
257
12.2.3
VEGF and Tumor Cells
258
12.2.4
Metastasis and VEGF Selectivity
258
12.3
Drag Selectivity
259
12.3.1
VEGF-Targeted Approaches
259
12.3.1.1
Specificity of Anti-VEGF Monoclonal Antibodies: Are Toxicities
Related to the Absence of Selectivity?
259
12.3.1.2
Association with Cytotoxics: Loss of Specificity or Increase of Drug
Targeting?
262
12.3.1.3
Paradoxical Specificity against Antiproliferative Targets?
263
12.3.1.4
VEGF-Trap
264
Xli Contents
12.3.2
Kinases
Signaling Pathways as a Target for Antiangiogenic
Activity
264
12.3.3
Non-VEGF/VEGFR Inhibition
266
12.3.3.1
HIF-la Inhibition
266
12.3.3.2
Notch Inhibition
267
12.4
Conclusion
268
References
269
Part V Imaging and
Biomarkers
in Angiogenesis
275
13
In vivo Imaging of Tumor Angiogenesis
277
Baris
Turkbey, Gregory Ravizzini, and Peter L. Choyke
13.1
Introduction
277
13.2
Mechanisms of Tumor Angiogenesis
277
13.3
Imaging
278
13.3.1
Ex vivo Tumor Imaging
278
13.3.2
In vivo Imaging Techniques
279
13.3.3
Targeted Imaging Techniques
284
13.3.3.1
Targeted Imaging of VEGF and VEGFR-2
285
13.3.3.2
Targeted Imaging of
Integrins
287
13.3.3.3
Targeted Imaging of MMPs
290
13.3.3.4
Targeted Imaging of the Extracellular Matrix (ECM)
290
13.4
Conclusion
291
References
29І
14
Identifying
Biomarkers
to Establish Drug Efficacy
299
J.
Suso
Platem
14.1
Introduction
299
14.1.1
Biomarkers
299
14.1.2
Biomarkers
in Drug Development
300
14.2
Pathway Analysis as a Tool to Identify
Biomarkers
301
14.3
Transcriptional Profiling as a Way to Find
Biomarkers
301
14.4
Finding
Biomarkers
through the Use of Cell Lines
303
14.4.1
Sprycel
303
14.4.2
Yondelis
304
14.5
Finding
Biomarkers
through the Use of Xenografts
305
14.5.1
Avastin
305
14.5.2
Sunitinib
306
14.5.3
Brivanib
306
14.6
Toxicity
Biomarkers
308
14.7
Imaging as
a Biomarker
309
14.7.1
Avastin
309
14.7.2
Sorafenib
309
14.8
Finding and Validating
Biomarkers
in Clinical Trials
310
14.8.1
Pharmacodynamic Markers
310
Contents XIII
14.8.1.1
EGFR Inhibitors
310
14.8.1.2
Sunitinib 311
14.8.1.3
Brivanib 311
14.8.2
Predictive Markers
313
14.8.2.1
Herceptin 313
14.8.2.2
Brivanib 314
14.8.2.3
EGFR Inhibitors
315
14.9
Conclusions
317
References
317
Index 321
Covering one of the most important research topics in cancer biology,
Tumor
Anţpogpnesis
is an ideal ready reference for oncologists, cell biologists,
pharmaceutical chemists, pathologists, molecular biologists, internists,
and researchers working in the pharmaceutical industry.
Following an introduction that provides an overview of tumor angiogenesis,
the book goes on to look at mechanisms of angiogenesis and lymphangio-
genesis, signal transduction, therapeutic approaches in combination with
established treatments, and concludes with a section on imaging and bio-
markers in angiogenesis.
Francis S.
Markland
is Professor of Biochemistry and Molecular Biology
at the University of Southern California, Keck School of Medicine. He ob¬
tained his PhD from Johns Hopkins University in
1964
and did his early
training at UCLA. Dr.
Markland
has been characterizing snake venom
proteins and examining their therapeutic potential for a number of years.
Most recently he and members of his laboratory have been studying the
anti-angiogenic and anti-tumor properties of
a
peptide
(member of the
disintegrin class) purified from southern copperhead venom; a modified
version of this
peptide
and other structurally related disintegrins are now
being produced by
recombinant
technology. The translational potential
of these peptides is presently being examined.
Stephen Swenson is an Assistant Research Professor of Biochemistry and
Molecular Biology at the University of Southern California, Keck School
of Medicine. He obtained his PhD in Biochemistry and Biophysics from
the University of Hawaii in
1995.
For his postgraduate training he joined
the
Markland
laboratory working on the characterization and evaluation
of direct acting thrombolytic enzymes from snake venom. Recently
Dr. Swenson has been pursuing the development of an anti-tumor and
anti-angiogenic agent based on snake venom disintegrins and disintegrin
domains of human ADAM proteins.
Radu
Minea
is a Senior Research Associate in the
Markland
laboratory
at the University of Southern California, Keck School of Medicine. He
obtained an
M D
degree from the Carol
Davila
School of Medicine in
Bucharest, Romania in
1993
and did his residency in general surgery in
Bucharest. Dr.
Minea
joined the
Markland
laboratory in
2002
and his
research involved the
recombinant
production of disintegrins for which he
conceived a unique approach designed to successfully address the complex
folding issues of this promising class of polypeptides. His current research
interest is aimed at exploring the translational potential of
recombinant
disintegrins and their novel clinical applications. |
| any_adam_object | 1 |
| author_GND | (DE-588)141164239 |
| building | Verbundindex |
| bvnumber | BV025605704 |
| classification_rvk | XH 1800 |
| ctrlnum | (OCoLC)637050370 (DE-599)BVBBV025605704 |
| dewey-full | 616.994071 |
| dewey-hundreds | 600 - Technology (Applied sciences) |
| dewey-ones | 616 - Diseases |
| dewey-raw | 616.994071 |
| dewey-search | 616.994071 |
| dewey-sort | 3616.994071 |
| dewey-tens | 610 - Medicine and health |
| discipline | Medizin |
| format | Book |
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| genre | (DE-588)4143413-4 Aufsatzsammlung gnd-content |
| genre_facet | Aufsatzsammlung |
| id | DE-604.BV025605704 |
| illustrated | Illustrated |
| indexdate | 2024-07-20T10:34:58Z |
| institution | BVB |
| isbn | 9783527320912 3527320911 |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-020200838 |
| oclc_num | 637050370 |
| open_access_boolean | |
| owner | DE-11 DE-355 DE-BY-UBR |
| owner_facet | DE-11 DE-355 DE-BY-UBR |
| physical | XXII, 329 S. Ill., graph. Darst. |
| publishDate | 2010 |
| publishDateSearch | 2010 |
| publishDateSort | 2010 |
| publisher | Wiley-VCH |
| record_format | marc |
| spelling | Tumor angiogenesis from molecular mechanisms to targeted therapy ed. by Francis S. Markland ... Weinheim Wiley-VCH 2010 XXII, 329 S. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier Tumorwachstum (DE-588)4186432-3 gnd rswk-swf Angiogenese (DE-588)4142449-9 gnd rswk-swf (DE-588)4143413-4 Aufsatzsammlung gnd-content Tumorwachstum (DE-588)4186432-3 s Angiogenese (DE-588)4142449-9 s DE-604 Markland, Francis S. 1936- Sonstige (DE-588)141164239 oth text/html http://deposit.dnb.de/cgi-bin/dokserv?id=3385120&prov=M&dok_var=1&dok_ext=htm Inhaltstext Digitalisierung UB Regensburg application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=020200838&sequence=000005&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis Digitalisierung UB Regensburg application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=020200838&sequence=000006&line_number=0002&func_code=DB_RECORDS&service_type=MEDIA Klappentext |
| spellingShingle | Tumor angiogenesis from molecular mechanisms to targeted therapy Tumorwachstum (DE-588)4186432-3 gnd Angiogenese (DE-588)4142449-9 gnd |
| subject_GND | (DE-588)4186432-3 (DE-588)4142449-9 (DE-588)4143413-4 |
| title | Tumor angiogenesis from molecular mechanisms to targeted therapy |
| title_auth | Tumor angiogenesis from molecular mechanisms to targeted therapy |
| title_exact_search | Tumor angiogenesis from molecular mechanisms to targeted therapy |
| title_full | Tumor angiogenesis from molecular mechanisms to targeted therapy ed. by Francis S. Markland ... |
| title_fullStr | Tumor angiogenesis from molecular mechanisms to targeted therapy ed. by Francis S. Markland ... |
| title_full_unstemmed | Tumor angiogenesis from molecular mechanisms to targeted therapy ed. by Francis S. Markland ... |
| title_short | Tumor angiogenesis |
| title_sort | tumor angiogenesis from molecular mechanisms to targeted therapy |
| title_sub | from molecular mechanisms to targeted therapy |
| topic | Tumorwachstum (DE-588)4186432-3 gnd Angiogenese (DE-588)4142449-9 gnd |
| topic_facet | Tumorwachstum Angiogenese Aufsatzsammlung |
| url | http://deposit.dnb.de/cgi-bin/dokserv?id=3385120&prov=M&dok_var=1&dok_ext=htm http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=020200838&sequence=000005&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=020200838&sequence=000006&line_number=0002&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT marklandfranciss tumorangiogenesisfrommolecularmechanismstotargetedtherapy |